Evidence map›Paper›PMID 41581643›Full record

ArticleCancer letters2026

Targeting the DDX3/PAF1 axis enhances chemotherapy efficacy in pancreatic ductal adenocarcinoma.

Palanisamy Nallasamy, Parthasarathy Seshacharyulu, Sanchita Rauth, Ashu Shah, Saravanakumar Marimuthu, Venkatesh Varadharaj, Madhulatha Bommideni, Kavita Mallya, Zahraa Wajih Alsafwani, Subodh M Lele and 3 more

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Article in Cancer letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Palanisamy NallasamyDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Parthasarathy SeshacharyuluDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Sanchita RauthDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Ashu ShahDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Saravanakumar MarimuthuDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Venkatesh VaradharajDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Madhulatha BommideniDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Kavita MallyaDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Zahraa Wajih AlsafwaniDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Subodh M LeleDepartment of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Venu RamanDepartment of Radiology and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Surinder K BatraDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA; Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address: sbatra@unmc.edu.
Moorthy P PonnusamyDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA; Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address: mpalanim@unmc.edu.

Funding

Pancreatic Cancer Detection ConsortiumU01CA210240 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Michael A. Hollingsworth · 2017 to 2026
$12.9M
Validation of biomarkers for risk prediction and early diagnosis of Pancreatic AdenocarcinomaU01CA200466 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Surinder K. Batra, Randall Brand · 2016 to 2026
$11.3M
Project 3: MUC16-Mediated Metabolic Reprograming Induces PC MetastasisP01CA217798 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI THAYER, SARAH P · 2018 to 2022
$8.1M
Truncated O-glycan-dependent mechanisms inducing metastatic dissemination in pancreatic cancerR01CA273349 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., PONNUSAMY, MOORTHY P. · 2022 to 2025
$2.7M
Molecular Imaging Probe(s) for Optical Surgical Navigation of Pancreatic CancerR01CA256973 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Surinder K. Batra, Michael Bouvet · 2022 to 2026
$2.2M
Connectivity mapping identified novel combination therapy for glioblastomaR01CA273319 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., SHONKA, NICOLE · 2022 to 2025
$2.2M
Novel Therapy to Inhibit IPMN ProgressionR01CA263575 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI BATRA, SURINDER K., MALAFA, MOKENGE P. · 2022 to 2024
$2.1M
Role of PD2/Paf1 in Pancreatic Acinar to Ductal MetaplasiaR01CA210637 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., PONNUSAMY, MOORTHY P. · 2017 to 2021
$2.0M
Targeting CXCR2 axis in Pancreatic CancerR01CA228524 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., SINGH, RAKESH K · 2018 to 2022
$2.0M
Rac1 GTPase in tumorigenesis and progression of pancreatic cancerR01CA206444 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., OUELLETTE, MICHEL M · 2016 to 2020
$1.9M
NCI NIH HHS P01 CA217798NCI NIH HHS R01 CA206444NCI NIH HHS R01 CA210637NCI NIH HHS R01 CA228524NCI NIH HHS R01 CA256973NCI NIH HHS R01 CA263575NCI NIH HHS R01 CA273319NCI NIH HHS R01 CA273349NCI NIH HHS U01 CA200466NCI NIH HHS U01 CA210240
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that has a poor survival rate of ∼13 % with limited options for effective therapies. DDX3 is a member of the DEAD-box RNA helicase enzyme family. It acts as an adapter protein that interacts with several transcription factors, enhancing their binding ability to the promoters of genes involved in cancer progression. Previously, we demonstrated that PAF1, a component of the RNA polymerase II-associated factor 1 complex, interacts with DDX3 to promote PDAC stemness. Here, we investigated the therapeutic efficacy of RK-33, a small-molecule inhibitor targeting DDX3, in combination with gemcitabine (GEM) and 5-fluorouracil (5FU), which enhanced therapeutic efficacy in KRAS-driven PDAC.-DDX3 and PAF1 exhibit progressively increased expression in various stages and correlate well with poor survival of PDAC. Targeting DDX3/PAF1 significantly mitigated clonogenic, EMT, and stemness phenotypes in PDAC cells. It also reduced tumor growth, proliferation, and increased apoptosis in xenograft and PDAC organoid models. Finally, MXRA5, EDIL3, COL13A1, and SLC16A2 were identified as top downstream response genes upon RK-33 treatment and potential new targets to mitigate extracellular matrix remodeling, angiogenesis, cell migration, and cell cycle progression, thereby enhancing the therapeutic efficacy of GEM and 5FU Overall, our data indicate that RK-33 enhances the therapeutic efficacy of GEM and 5FU in mitigating PDAC aggressiveness. Consequently, these findings open new avenues for developing efficacious therapeutic adjuvants to treat advanced pancreatic cancer.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsCarcinoma, Pancreatic DuctalDEAD-box RNA HelicasesNuclear ProteinsPancreatic NeoplasmsAnimalsApoptosisCell Line, TumorCell MovementCell ProliferationDeoxycytidineEpithelial-Mesenchymal TransitionFluorouracilGemcitabineGene Expression Regulation, NeoplasticHumansDDX3X protein, humanDEAD-box RNA HelicasesDeoxycytidineFluorouracilGemcitabineNuclear ProteinsPAF1 protein, humanTranscription Factors

Identifiers

PMID41581643
PMCPMC13105205

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.